A systematic and integrated investigation of hepatic protein metabolism in the rat is being conducted using the whole animal, the perfused liver and isolated hepatocytes as experimental models. The effects of fasting and selective refeeding are being studied to define the nature of the nutritional regulation of albumin and liver protein turnover. Hormone deprivation, supplementation, and interactions are being examined in the case of insulin, growth hormone, thyroxine, and glucocorticoids. An integrated approach is being carried out at the molecular level to quantitate the roles of: amino acid transport and substrate availability; the size, distribution and quantity of total, membrane-bound, and free liver polysomes; the quantity and distribution of total free ribosome monomers and subunits; and the quantitation of specific albumin-synthesizing polysomes and mRNA. Changes in these parameters are used to localize sites of regulation of protein and albumin synthesis. Rates of protein degradation are also being examined. An emphasis is placed on how the nutritional and hormonal environment of the liver cell controls protein metabolism and thereby regulates liver function.